MOTIVATION - Diffusion Tensor Imaging (DTI) is an MRI method for noninvasive quantitative mapping of anisotropic water diffusion, thereby allowing the investigation of white matter (WM) microstructure. DTI holds tremendous potential for aiding the understanding of pathophysiologies of white matter and delayed maturation. In addition, it enables non-invasive tracing of WM pathways in tumor patients and is also helpful for diagnosing patients harboring non-focal disease. However, DTI still suffers from technical shortcomings which become even more problematic with increasing magnetic fields. This is unfortunate since increased magnetic field strengths offer substantially more SNR that is desperately needed for an SNR-starved method such as DTI. Because of their size and other specific requirements, especially pediatric patients would be major benefactors from DTI high field imaging - particularly when combined with more powerful fMRI and structural imaging achievable at these higher fields. Obstacles to using DTI at higher fields include: FOV requirements, lack of cooperation, increased motion, increase off-resonance artifacts, significant RF inhomogeneity, and increased RF energy deposition. AIMS - The main objective of the proposed project is to create significant improvements in DTI at high field (i.e. 3T and 7T) via novel acquisition/reconstruction techniques that reduce distortions, improve immunity to motion, diminish RF deposition and flip angle variation, and provide better spatial resolution so that improved pediatric and adult high-field DTI is enabled. The specific aims are to develop and optimize acquisition and reconstruction methods for diffusion tensor short-axis-readout EPI (sr-EPI) (A.1), and investigate and help to rekindle interest in 7T DTI by incorporating optimized sr-EPI DTI sampling strategies with parallel transmit as well as to further boost scan efficiency by adding multi-echo readouts (A.2). Anticipating the move toward higher-field strengths, these aims are designed to provide a robust imaging protocol for the clinical environment (3T), while providing the means to overcome short-comings in current ultra-high field strength methodologies. METHODS - In A.1, novel schemes for off-resonance, eddy-current, and motion correction will be developed. In addition, an efficient parallel imaging reconstruction algorithm will be developed to compliment a family of proposed SNR-, SAR-, and scan time-efficient sr-EPI techniques. In A.2, work with an experienced group of collaborators will allow the implementation of parallel transmit technology on our 7T. Together with an 'exact'distortion model, these B1/B0 correction methodologies ideally compliment a fast variant of sr-EPI. By adding RF-refocused multi-blade/blind readout the scan efficiency will be increased even further. All proposed acquisition and reconstruction techniques will be optimized both in simulations and phantom studies. A total number of subjects of 200 (children and adults) will be enrolled over this five year period for extensive testing. Optimal image quality will be determined by quantitative metrics and human observers. SIGNIFICANCE -We believe successful attainment of these aims promises to significant improvements in DTI, reaching beyond high field and pediatric patients, and hence greater overall utility of DTI. Abnormalities in WM and tract projections could provide crucial insights in the pathophysiology of several diseases that attack white matter, and further the understanding of specific neurodevelopmental trajectories of children with and without WM disorders. The success of our research effort would be of great value since it would build the basic methodological framework at high field for further clinically focused studies and basic neuroscience research.